Exposure to an uncontrollable aversive event can elicit a strong analgesia in rats. This analgesia appears to be opioid in nature, since it is blocked by both opioid antagonists and morphine tolerance. Moreover, the analgesia exhibits both tolerance (decreases with repeated exposure) and cross-tolerance with morphine. This example of opioid analgesia seems "hormonal" in nature since it is blocked by manipulations which disrupt the functioning of the pituitary-adrenal axis. Prior work has shown that activating the hormonal opioid system not only attenuates pain, but also suppresses immune function. Clinically, this means that activating the hormonal opioid system might benefit a person in pain, but be detrimental to a person whose immune system is dysfunctional. In order to take advantage of the benefits of activating the hormonal opioid system, and to avoid its detrimental consequences, we need to define the conditions under which the system is activated. We have previously shown that the psychological variable of control is an important determinant of whether or not the hormonal opioid system is activated. Specifically, we have demonstrated that exposure to uncontrollable shock, but not controllable shock, activates the hormonal opioid system. In the past, we have assumed that this effect required exposure to an aversive event. However, a recent study suggests that this may not be necessary. Specifically, Tazi, Dantzer and LeMoal (1987) have reported that exposure to uncontrollable, but not controllable, appetitive reinforcement (food) induces a strong analgesia in rats. However, it remains unclear whether this analgesia is mediated by the hormonal opioid system. The studies proposed here will resolve this issue. We will determine whether the analgesia elicited by exposure to uncontrollable appetitive reinforcement is opioid in nature by determining whether the analgesia exhibits tolerance and cross- tolerance with morphine. In addition, we will test whether the analgesia can be blocked by an opioid antagonist. We will test whether the analgesia is hormonal in nature by assessing the impact of two manipulations which disrupt the functioning of the pituitary-adrenal axis: administration of dexamethasone and adrenalectomy.